The semaphorins constitute a family of secreted and transmembrane molecules that serve as repulsive guidance cues for developing neurons by virtue of their ability to induce retracton of the axonal growth cones. The functions of semaphorins are mediated plexins. Out of plexins, plexinB binds Sema4D, a class 4 transmembrane semaphorin, and mediate its signals via the Rho family GTPase. 1)In this project, we first found that PDZ domain containing-RhoGEFs associate plexinB1 and B2, to mediate Sema4D signal to activate RhoA (ref 1). 2)Recently, semaphorins are implicated in many physiological functions, in addition to repulsive roles in axon guidance. Second, we identified that Sema4D had ability to induce extension of axonal growth (ref 2 and 3). PC12 cells and spinal ganglion neurons respond to Sema4D and stimulated extension of axons, when cells were cultured with added NGF, and when spinal ganglion neurons were cultured without antibodies against NGF that bind endogenous NGF to block NGF-action. Since spinal ganglion neurons express Sema4D and plexinB1, Sema4D appeared to function in an autocrine manner in these neurons. These results suggest that some semaphorin can also functions as attractive guidance cues. 3)Third, we identified PDZ-containing Rho-GEFs associate to LPA1 and LPA2 but not LPA3, GPCR type receptors for lisophophatidic acid(LPA), a serum-derived phospholipid (ref 8). LPA has ability to retract axonal growth. Our results suggest that PDZ-containing Rho-GEFs couples GPCRs and plexinB1 to mediate LPA signals as well as Sema4D signals, and suggest a future study in situ function in the brain. 4)We found that glia cells expressed plexinB1 and Sema4D was implicated in regulation of glial activation, suggesting that an important role of Sema4D by regulating glial function.